Experimental animals were studied under gnotobiotic conditions or in isolation to evaluate virulence of selected human and animal rotavirus strains as well as to study homologous and heterologous immunity. Gnotobiotic piglets were studied although gnotobiotic calves had been used extensively in the past. In a previous study of heterologous immunity, we demonstrated that in utero inoculation with bovine rotavirus protected calves against challenge with human rotavirus of a distinct serotype. Recent reevaluation of the calf sera from this study indicated that a single exposure to bovine rotavirus induced broadly reactive neutralizing antibody, which may explain the observed heterologous immunity. In a study of homologous immunity, piglets were exposed to human rotavirus "Wa" in utero and again at birth. Control animals without prior exposure to rotavirus shed significantly more virus and tended to have more diarrhea than those inoculated in utero. In an additional study piglets were inoculated post-natally with rhesus rotavirus and subsequently challenged with human rotavirus ("M" strain) to look for immunity between those related strains. Such prior rotavirus infection diminished viral shedding when piglets were challenged with human rotavirus ("M" strain). Experimental animal systems now exist for the evaluation of cross-immunity between rotavirus strains, and these studies should aid in the selection of appropriate vaccine strains.